Project summary/Abstract Human greater saphenous vein (HSV) is the most commonly used conduit for coronary artery bypass grafting (CABG) and the most effective conduit for infrainguinal peripheral vascular bypass grafting (PVBG). However, the rate of vein graft failure remains high (45% at 1-11/2 years) and there is no current therapeutic approach that has yet been shown to reduce vein graft failure in humans. HSV is harvested from the extremity and prepared prior to implantation. During this process, surgeons typically manually stretch and distend the HSV, store the conduit in heparinized saline, and mark the vein to prevent twisting or kinking on implantation. These maneuvers cause significant injury to the cellular components of the conduit which leads to intimal hyperplasia and vein graft failure. HSV represents an autologous organ that is transplanted into the arterial circulation. Despite the many advances in organ preservation, the current techniques used to prepare and preserve HSV do not adequately protect the transplanted vein. The hypothesis of this proposal is that injury to the cellular components of HSV during preparation lead to intimal hyperplasia and vein graft failure. The corollary to this hypothesis is that minimizing injury at the time of surgical preparation will impact subsequent vein graft patency. This proposal will develop elegantly simple approaches to prevent injury during graft preparation as well as promote our understanding of the processes that lead to vein graft intimal hyperplasia. The potential impact of this proposal is to develop optimal vein preparation techniques that can be readily translated into the clinic thus reducing the morbidity, mortality, and costs associated with vein graft failure.